US2025099482A1PendingUtilityA1
Tip60 neuro-epigenetic modulators
Est. expirySep 22, 2043(~17.1 yrs left)· nominal 20-yr term from priority
A61K 31/437A61K 31/341A61K 31/415A61K 31/5375A61P 25/28A61K 31/136A61K 31/444A61K 31/4196A61K 31/381A61K 31/4985A61K 31/47A61K 31/551A61K 31/167
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Claims
Abstract
The present disclosure relates, in part, to compounds, compositions, and methods for treatment, ameliorating, and/or prevention of certain neurodegenerative diseases and/or cancers.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of treating, preventing, or ameliorating a neurodegenerative disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of at least one Tip60 activator or a pharmaceutically acceptable salt thereof.
2 . The method of claim 1 , wherein the neurodegenerative disease is at least one selected from the group consisting of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia, Multiple System Atrophy, Progressive Supranuclear Palsy, Corticobasal Degeneration, Lewy Body Dementia, Friedreich's Ataxia, Spinocerebellar Ataxia, Spinal Muscular Atrophy, Prion Diseases (such as Creutzfeldt-Jakob Disease), Wernicke-Korsakoff Syndrome, Kennedy's Disease (Spinal Bulbar Muscular Atrophy), Wilson's Disease, Niemann-Pick Disease, and Gerstmann-Sträussler-Scheinker Syndrome (GSS).
3 . The method of claim 1 , wherein the neurodegenerative disease is at least one selected from the group consisting of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis (ALS).
4 . The method of claim 1 , wherein the subject is further administered at least one additional agent suitable for the treatment, prevention, or amelioration of a neurodegenerative disease.
5 . The method of claim 1 , wherein the Tip60 activator is a compound of Formula (I) or a pharmaceutically acceptable salt thereof:
wherein:
R 1a , R 1b , and R 1e are each independently selected from the group consisting of H, optionally substituted C 1 -C 6 alkyl, halogen, CN, and NO 2 ;
R 1c is halogen;
R 1d is C 1 -C 3 haloalkyl;
R 2 is selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl;
R 3a and R 3e are each independently selected from the group consisting of optionally substituted C 1 -C 12 alkoxy and optionally substituted C 1 -C 20 alkyl; and
R 3b , R 3c , and R 3d are each independently selected from the group consisting of H, optionally substituted C 1 -C 6 alkyl, halogen, CN, and NO 2 .
6 . The method of claim 5 , wherein at least one of the following applies:
(a) R 1a , R 1b , and R 1e are each independently H; (b) R 1c is Cl; (c) R 1d is CF 3 ; and (d) R 2 is H.
7 . The method of claim 5 , wherein R 3c is selected from the group consisting of OEt, OiPr,
8 . The method of claim 5 , wherein R 3c is selected from the group consisting of H, (CH 2 ) 14 CH 3 , and O(CH 2 ) 2 N(CH 3 ) 2 .
9 . The method of claim 5 , wherein the compound of Formula (I) is selected from the group consisting of:
10 . The method of claim 1 , wherein the Tip60 activator is a compound of Formula (II) or a pharmaceutically acceptable salt thereof:
wherein:
R 4 is selected from the group consisting of optionally substituted C 2 -C 8 heteroaryl and C 6 -C 10 aryl;
R 5 is selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl;
R 6a and R 6b are each independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl;
R 7 is selected from the group consisting of H, optionally substituted C 1 -C 6 alkyl, halogen, CN, and NO 2 ;
R 8 is selected from the group consisting of H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 2 -C 8 heterocycloalkyl, and C(═O)N(R A )(R B );
L 1 is —[C(R 9a )(R 9b )] 1-2 —;
L 2 is —[C(R 10a )(R 10b )] 1-2 -;
each occurrence of R 9a and R 9b is independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl;
each occurrence of R 10a and R 10b is independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl; and
R A and R B are each independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl, or R A and R B combine with the N atom to which they are bound to form an optionally substituted C 2 -C 8 heterocycloalkyl.
11 . The method of claim 10 , wherein at least one of the following applies:
(a) R 4 is selected from the group consisting of
(b) R 5 is H;
(c) R 6a and R 6b are each independently H;
(d) R 7 is H;
(e) R 8 is selected from the group consisting of cyclohexyl and C(═O)N(CH 3 ) 2 ;
(f) L 1 is —CH 2 —;
(g) L 2 is selected from the group consisting of —(CH 2 ) 2 — and —(CH 2 ) 3 —.
12 . The method of claim 10 , wherein the compound of Formula (II) is selected from the group consisting of:
13 . The method of claim 1 , wherein the Tip60 activator is selected from the group consisting of:
14 . A method of treating, preventing, or ameliorating a Tip60-dependent cancer or Tip60-overexpressing cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of a Tip60 inhibitor or a pharmaceutically acceptable salt thereof.
15 . The method of claim 14 , wherein the Tip60 activator is a compound of Formula (I) or a pharmaceutically acceptable salt thereof:
wherein:
R 1a , R 1b , and R 1e are each independently selected from the group consisting of H, optionally substituted C 1 -C 6 alkyl, halogen, CN, and NO 2 ;
R 1c is halogen;
R 1d is C 1 -C 3 haloalkyl;
R 2 is selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl;
R 3a and R 3c are each independently selected from the group consisting of optionally substituted C 1 -C 12 alkoxy and optionally substituted C 1 -C 20 alkyl; and
R 3b , R 3c , and R 3d are each independently selected from the group consisting of H, optionally substituted C 1 -C 6 alkyl, halogen, CN, and NO 2 .
16 . The method of claim 14 , wherein the Tip60 activator is a compound of Formula (II) or a pharmaceutically acceptable salt thereof:
wherein:
R 4 is selected from the group consisting of optionally substituted C 2 -C 8 heteroaryl and C 6 -C 10 aryl;
R 5 is selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl;
R 6c and R 6b are each independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl;
R 7 is selected from the group consisting of H, optionally substituted C 1 -C 6 alkyl, halogen, CN, and NO 2 ;
R 8 is selected from the group consisting of H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 2 -C 8 heterocycloalkyl, and C(═O)N(R A )(R B );
L 1 is —[C(R 9a )(R 9b )] 1-2 —;
L 2 is —[C(R 10a )(R 10b )] 1-2 —;
each occurrence of R 9c and R 9b is independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl;
each occurrence of R 10 a and R 10b is independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl; and
R A and R B are each independently selected from the group consisting of H and optionally substituted C 1 -C 6 alkyl, or R A and R B combine with the N atom to which they are bound to form an optionally substituted C 2 -C 8 heterocycloalkyl.
17 . The method of claim 14 , wherein the Tip60 activator is selected from the group consisting of:
18 . The method of claim 14 , wherein the Tip60-dependent or Tip60-overexpressing is at least one selected from the group consisting of breast cancer, prostate cancer, colorectal cancer, lung cancer, ovarian cancer, glioblastoma, hepatocellular carcinoma, gastric cancer, leukemia, melanoma, pancreatic cancer, bladder cancer, cervical cancer, esophageal cancer, head and neck squamous cell carcinoma, renal cell carcinoma, thyroid cancer, non-small cell lung cancer, endometrial cancer, and lymphoma.
19 . The method of claim 14 , wherein the subject is further administered at least one additional agent suitable for the treatment, prevention, or amelioration of cancer.
20 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound selected from the group consisting of:Join the waitlist — get patent alerts
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